Objective:To investigate the iodine nutrition level and thyroid function status of pregnant women in Hubei Province.Methods:According to the requirements of "the National Iodine Deficiency Disorders Monitoring Program (2016 Edition)", in 2020, using a cross-sectional survey method, two mountainous counties and two plain areas in Hubei Province were divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) as survey subjects. Urine iodine content and thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] were tested. Abnormal thyroid function rate and antibody positive rate were analyzed, and correlation analysis of thyroid function indicators was conducted (Spearman method). Results:A total of 321 pregnant women were included, including 43, 114, and 164 in early, middle, and late pregnancy, respectively; The median urinary iodine was 164.80 μg/L. The median serum FT 3, FT 4, TSH, TPOAb, TgAb levels were 4.10, 12.83 pmol/L, 1.85 mU/L, 15.84 and 13.35 U/ml, respectively. There were statistically significant differences in FT 3, FT 4, and TSH levels among different trimesters ( P < 0.05). According to Spearman's correlation analysis, FT 3 in early stage of pregnancy was negatively correlated with TSH and TPOAb levels ( r = - 0.46, - 0.33, P < 0.05), while TSH was positively correlated with TPOAb level ( r = 0.33, P = 0.032); there was a positive correlation between FT 4 and TgAb levels in middle stage of pregnancy ( r = 0.21, P = 0.032); there was a negative correlation between FT 3 and TPOAb levels in late stage of pregnancy ( r = - 0.19, P = 0.017); FT 3 and FT 4, TPOAb and TgAb levels were positively correlated throughout pregnancy ( P < 0.05). There was no correlation between urinary iodine content and thyroid function indicators ( P > 0.05). The total abnormal rate of thyroid function was 7.79% (25/321), with 16.28% (7/43), 5.26% (6/114), and 7.32% (12/164) in early, middle, and late pregnancy, respectively. There was no statistically significant difference in the abnormal rate of thyroid function among different pregnancy periods (χ 2 = 4.83, P = 0.097). The detection rates of hypothyroxinemia, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism were 4.36% (14/321), 0.31% (1/321), 2.49% (8/321), 0.31% (1/321), and 0.31% (1/321), respectively. The positive detection rate of autospecific antibodies was 10.28% (33/321), with a TPOAb positive detection rate of 9.97% (32/321) and a TgAb positive detection rate of 5.30% (17/321). Conclusions:The iodine nutrition level of pregnant women in Hubei Province is at a suitable level, and the rates of abnormal thyroid function and thyroid autospecific antibody positive are relatively low. It is necessary to continuously monitor the iodine nutrition and thyroid function indexes of pregnant women, strengthen health education on the hazards of iodine deficiency during pregnancy, and minimize the harm to maternal and infant health caused by iodine deficiency.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
Humans ; Mice ; Animals ; Dysbiosis ; Anti-Bacterial Agents/pharmacology* ; Virulence ; Microbiota ; Periodontitis/chemically induced* ; Cytokines

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate (4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time, the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2^-/- mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment. Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction, ameliorate local inflammation for more predictable periodontitis.
Alveolar Bone Loss/prevention & control* ; Animals ; Antioxidants/pharmacology* ; Inflammation ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; NF-E2-Related Factor 2/metabolism* ; Periodontitis/prevention & control* ; Succinates

Objective:To investigate the mechanism underlying the inhibiting effect of low-glucose combined with palmitic acid on human colon cancer cells and its influence on the radiosensitivity.Methods:Under the treatment of low-glucose, palmitic acid and low-glucose combined with palmitic acid, the treatment condition that significantly inhibited the proliferation of SW480 was screened by CCK-8 assay. The reactive oxygen species (ROS) level, mitochondrial membrane potential and apoptosis rate were detected by flow cytometry. The changes in the radiosensitivity were detected by immunofluorescence-based γ-H 2AX quantification and colony formation assay. The protein expression level was detected by Western blot. Results:Compared with the control group, the condition of low-glucose combined with 120μmol/L palmitic acid significantly inhibited the proliferation of SW480 cells ( P<0.01). The expression levels of CPT1a, PFKFB3 and PKM were significantly up-regulated, the expression levels of NDUFV1, NDUFV2 and NDUFS1 were remarkably down-regulated, the ROS level was significantly increased and the ATP level was considerably reduced in the cells under metabolic stress (all P<0.01). After irradiation, the number of γ-H 2AX foci was significantly increased ( P<0.05), and the D 0 value was significantly reduced ( P<0.01), the ROS level was considerably increased ( P<0.001), the apoptosis rate was significantly increased ( P<0.001) and the expression level of γ-H 2AX protein was remarkably up-regulated ( P<0.01) in the low-glucose combined with 120μmol/L palmitic acid group. Pretreatment with NAC could reverse the changes of ROS, apoptosis and γ-H 2AX protein expression. Conclusions:The combination of low-glucose and palmitic acid can induce metabolic stress in SW480 cells, inhibit tumor proliferation and increase the radiosensitization when combined with radiotherapy by inducing the generation of ROS and DNA damage.

An increasing number of studies have recently indicated the important effects of gut microbes on various functions of the central nervous system.However, the underlying mechanisms by which gut microbiota regulate brain functions and behavioral phenotypes remain largely unknown. We therefore used isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis to obtain proteomic profiles of the hippocampus in germ-free (GF), colonized GF, and specific pathogen-free (SPF) mice. We then integrated the resulting proteomic data with previously reported mRNA microarray data, to further explore the effects of gut microbes on host brain functions. We identified that 61 proteins were upregulated and 242 proteins were downregulated in GF mice compared with SPF mice. Of these, 124 proteins were significantly restored following gut microbiota colonization. Bioinformatic analysis of these significant proteins indicated that the glucocorticoid receptor signaling pathway and inflammation-related pathways were the most enriched disrupted pathways. This study provides new insights into the pathological mechanisms of gut microbiota-regulated diseases.